Uranium has been mined for many years and used for fuel for nuclear reactors and materials for atomic weapons, ammunition, and armor. The radioactivity of uranium has been linked to the development of lung, kidney cancers, and leukemia. Little is known about the direct chemical genotoxicity of uranium. The purpose of the research is to gather more information about the chemical genotoxicity of uranium. The overall aims are to (1) identify the possible mechanisms induced by the chemical toxicity of uranium, (2) investigate the chemical effects of altered gene expression in HBE-16 cells, induced by exposure to depleted uranium as uranyl acetate, and (3) to determine the role of the altered genes in uranium carcinogenesis. The use of cDNA microarray to profile the gene expression of uranium-transformed cells in vitro will provide a picture as to what genes are being altered and pose questions regarding possible mechanisms of carcinogenesis. It is hypothesized that uranium will alter genes responsible for apoptosis and oncogene induction. Understanding how uranium reacts with DNA is important to better understand how this carcinogen induces cancer and to help to elucidate mechanisms of lung and other cancers in people exposed to uranium.